Prognostic value of TP53 expression and MGMT methylation in glioblastoma patients treated with temozolomide combined with other chemotherapies.

OBJECTIVE: To assess the recurrence interval and predictive significance of TP53 expression and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas treated with radiotherapy and combined chemotherapies, including temozolomide, lomustine, procarbazine and bevacizumab. METHOD: We reviewed the clinical outcomes of 52 totally resected glioblastoma patients, who received conventional radiotherapy and temozolomide with other chemotherapeutic agents. Correlation of TP53 expression and MGMT promotor methylation with recurrence interval was analyzed using Kaplan Meier estimates. RESULTS: No significant association was found between MGMT promotor methylation and TP53 expression in glioblastomas (P-value = 0.158). Patients with non-methylated MGMT who received temozolomide chemotherapy with other chemotherapeutic agents showed significantly later recurrence (P-value = 0.007) compared with patients with non-methylated MGMT who received temozolomide alone. No significant difference was found in recurrence interval among glioblastoma patients with methylated MGMT who received temozolomide alone or with other chemotherapies (P-value = 0.667). Moreover, patients with non-TP53-expressing tumors who received temozolomide with other chemotherapies had significantly later recurrence (P-value = 0.04) compared with patients who received temozolomide alone. CONCLUSION: Totally resected glioblastoma patients, with non-methylated MGMT or non-TP53-expressing tumors treated with radiotherapy and combined chemotherapies had a reduced chance of tumor recurrence and a more favorable outcome. Furthermore, both MGMT and TP53 are independent prognostic factors for glioblastoma.

Using Augmented Reality Technology to Optimize Transfacet Lumbar Interbody Fusion: A Case Report.

The transfacet minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a novel approach available for the management of lumbar spondylolisthesis. It avoids the need to manipulate either of the exiting or traversing nerve roots, both protected by the bony boundaries of the approach. With the advancement in operative technologies such as navigation, mapping, segmentation, and augmented reality (AR), surgeons are prompted to utilize these technologies to enhance their surgical outcomes. A 36-year-old male patient was complaining of chronic progressive lower back pain. He was found to have grade 2 L4/5 spondylolisthesis. We studied the feasibility of a trans-Kambin or a transfacet MIS-TLIF, and decided to proceed with the latter given the wider corridor it provides. Preoperative trajectory planning and level segmentation in addition to intraoperative navigation and image merging were all utilized to provide an AR model to guide us through the surgery. The use of AR can build on the safety and learning of novel surgical approaches to spine pathologies. However, larger high-quality studies are needed to further objectively analyze its impact on surgical outcomes and to expand on its application.

Advancing Prone-Transpsoas Spine Surgery: A Narrative Review and Evolution of Indications with Representative Cases.

The Prone Transpsoas (PTP) approach to lumbar spine surgery, emerging as an evolution of lateral lumbar interbody fusion (LLIF), offers significant advantages over traditional methods. PTP has demonstrated increased lumbar lordosis gains compared to LLIF, owing to the natural increase in lordosis afforded by prone positioning. Additionally, the prone position offers anatomical advantages, with shifts in the psoas muscle and lumbar plexus, reducing the likelihood of postoperative femoral plexopathy and moving critical peritoneal contents away from the approach. Furthermore, operative efficiency is a notable benefit of PTP. By eliminating the need for intraoperative position changes, PTP reduces surgical time, which in turn decreases the risk of complications and operative costs. Finally, its versatility extends to various lumbar pathologies, including degeneration, adjacent segment disease, and deformities. The growing body of evidence indicates that PTP is at least as safe as traditional approaches, with a potentially better complication profile. In this narrative review, we review the historical evolution of lateral interbody fusion, culminating in the prone transpsoas approach. We also describe several adjuncts of PTP, including robotics and radiation-reduction methods. Finally, we illustrate the versatility of PTP and its uses, ranging from 'simple' degenerative cases to complex deformity surgeries.

Evolution of the Transforaminal Lumbar Interbody Fusion (TLIF): From Open to Percutaneous to Patient-Specific.

The transforaminal lumbar interbody fusion (TLIF) has seen significant evolution since its early inception, reflecting advancements in surgical techniques, patient safety, and outcomes. Originally described as an improvement over the posterior lumbar interbody fusion (PLIF), the TLIF began as an open surgical procedure, that notably reduced the need for the extensive neural retractation that hindered the PLIF. In line with the broader practice of surgery, trending toward minimally invasive access, the TLIF was followed by the development of the minimally invasive TLIF (MIS-TLIF), a technique that further decreased tissue trauma and postoperative complications. Subsequent advancements, including Trans-Kambin's Triangle TLIF (percLIF) and transfacet LIF, have continued to refine surgical access, minimize surgical footprint, and reduce the risk of injury to the patient. The latest evolution, as we will describe it, the patient-specific TLIF, is a culmination of the aforementioned adaptations and incorporates advanced imaging and segmentation technologies into perioperative planning, allowing surgeons to tailor approaches based on individual patient anatomy and pathology. These developments signify a shift towards more precise methods in spine surgery. The ongoing evolution of the TLIF technique illustrates the dynamic nature of surgery and emphasizes the need for continued adaptation and refinement.

Using Novel Segmentation Technology to Define Safe Corridors for Minimally Invasive Posterior Lumbar Interbody Fusion.

BACKGROUND AND OBJECTIVES: There has been a rise in minimally invasive methods to access the intervertebral disk space posteriorly given their decreased tissue destruction, lower blood loss, and earlier return to work. Two such options include the percutaneous lumbar interbody fusion through the Kambin triangle and the endoscopic transfacet approach. However, without accurate preoperative visualization, these approaches carry risks of damaging surrounding structures, especially the nerve roots. Using novel segmentation technology, our goal was to analyze the anatomic borders and relative sizes of the safe triangle, trans-Kambin, and the transfacet corridors to assist surgeons in planning a safe approach and determining cannula diameters. METHODS: The areas of the safe triangle, Kambin, and transfacet corridors were measured using commercially available software (BrainLab, Munich, Germany). For each approach, the exiting nerve root, traversing nerve roots, theca, disk, and vertebrae were manually segmented on 3-dimensional T2-SPACE magnetic resonance imaging using a region-growing algorithm. The triangles' borders were delineated ensuring no overlap between the area and the nerves. RESULTS: A total of 11 patients (65.4 ± 12.5 years, 33.3% female) were retrospectively reviewed. The Kambin, safe, and transfacet corridors were measured bilaterally at the operative level. The mean area (124.1 ± 19.7 mm2 vs 83.0 ± 11.7 mm2 vs 49.5 ± 11.4 mm2) and maximum permissible cannula diameter (9.9 ± 0.7 mm vs 6.8 ± 0.5 mm vs 6.05 ± 0.7 mm) for the transfacet triangles were significantly larger than Kambin and the traditional safe triangles, respectively (P < .001). CONCLUSION: We identified, in 3-dimensional, the borders for the transfacet corridor: the traversing nerve root extending inferiorly until the caudal pedicle, the theca medially, and the exiting nerve root superiorly. These results illustrate the utility of preoperatively segmenting anatomic landmarks, specifically the nerve roots, to help guide decision-making when selecting the optimal operative approach.

Diagnostic Discrepancies Between Intraoperative Frozen Section and Permanent Histopathological Diagnosis of Brain Tumors.

OBJECTIVE: Intraoperative frozen section (IOFS) diagnosis of brain tumors plays an important role in assessing the adequacy of the sample and determining the treatment plan. The aim of this study was to investigate the diagnostic accuracy between IOFS and permanent sections. MATERIAL AND METHOD: The authors reviewed the histopathological results of 383 brain tumors, including IOFS and permanent histological diagnosis. The cases were classified into three diagnostic compatibilities (i) Perfect fit; the diagnosis of IOFS was identical to the permanent diagnosis, (ii) Partial compatibility; IOFS diagnosis was not incorrect but was too broad to be considered full compatibility, (iii) Conflict; IOFS diagnosis is completely different from the permanent diagnosis. The permanent diagnosis was used as a primary criterion and was compared to IOFS diagnosis and recurrence rate using different statistical methods. RESULTS: 84% of the patients underwent craniotomy and tumor resection, while 15% only underwent tumor biopsy. Approximately, 53.8 % of the cases revealed perfect matching in the diagnosis between IOFSs and permanent sections, while 16.2% of the cases revealed complete mismatching in the diagnosis between the sections. The remaining 30% of the cases showed partial compatibility in the diagnosis between the two diagnostic methods. There was no significant difference in recurrence rate among all cases of different diagnostic compatibility (p=0.54). CONCLUSION: There is a diagnostic discrepancy between IOFSs and permanent sections. However, cases that revealed no consensus in the diagnoses showed no negative effect on the patient outcome. Further studies should be conducted to explore the reasons of this conflict in the two diagnostic methods.

The Impact of Country Self-Citation Rate Among Medical Specialties in Saudi Arabia.

Objectives The purpose of the study was to evaluate the impact of country self-citation rate (SCR) among medical specialties in Saudi Arabia, and to assess the impact of self-citations on the country's total cites world ranking in different specialties. Methods SCImago Journal & Country Rank (SJR) was used to collect data related to all medical specialties in Saudi Arabia for the period 1996-2019. The country SCR for the specialties was correlated with several bibliometric parameters and examined statistically. The specialties that showed a drop in Saudi Arabia's total cites world ranking following the exclusion of self-citations were identified. Results The median country SCR for 46 specialties in Saudi Arabia was 9.5% (range: 4.6-23.1%). The two specialties with the highest country SCR were Public Health (23.1%) and Family Practice (22.9%). Country SCR was significantly higher in the non-clinical specialties compared to clinical specialties (15.3% vs. 9.6%). It did not correlate significantly with any of the examined productivity indices. The exclusion of self-citations resulted in a drop in Saudi Arabia's total cites world ranking in six (13%) specialties only. There was no significant difference between the country's total cites and net total cites world rankings in the specialties. Conclusions Self-citation may be appropriate and signify an expansion of the authors' previous work. Country SCR in medical specialties in Saudi Arabia is relatively low and not affected by total documents and total cites. Non-clinical specialties tend to self-cite more. The exclusion of self-citations had minimal effect on Saudi Arabia's total cites world ranking, indicating that country SCR in the specialties is unlikely to impact its international scientific standing. Our findings do not support the argument for eliminating self-citation from citation-based metrics. We believe that more collaborative and global research practices should be encouraged.

Impact of country self citation on the ranking of the top 50 countries in clinical neurology.

OBJECTIVES: To examine the factors that influence country self-citation rate (SCR) in clinical neurology and to assess the impact of self-citation on the ranking of the top 50 countries. METHODS: SCImago Journal & Country Rank was used to collect data for the 50 most cited countries in clinical neurology during 1996-2019. Country SCR was correlated with several productivity parameters and examined statistically. Countries that dropped in their ranking after the exclusion of self-citations were identified. RESULTS: The median (range) country SCR for the 50 most cited countries was 11.3%.(5.3%- 47%). Country SCR correlated significantly with total citable documents and total cites numbers and rankings. The exclusion of self-citations led to a drop in the ranking of 8(16%) countries only. No significant difference between the total and net total cites rankings was observed. CONCLUSIONS: Self-citation can be appropriate and reflect an expansion on earlier research. Highly cited productive countries tend to have high country SCR. Excluding self-citations had minimal impact on the ranking of the top 50 countries. Our findings indicate that self-citation is unlikely to influence country standing amongst the top 50 and does not support the argument for eliminating self-citations from citation-based metrics. A more globalization through international collaboration in research is encouraged.

Epidemiological distribution of primary central nervous system tumors in the Western Province of Saudi Arabia: a local registry from neuroscience-affiliated centers.

OBJECTIVES: Central nervous system (CNS) tumors are a major and growing global healthcare challenge. Western Saudi Arabia has an inconsistent data registry; therefore, the epidemiology of CNS tumors is unclear across the country. This study is aimed to assemble the epidemiological matrix of CNS tumors in the Western Province of Saudi Arabia. METHODS: A retrospective analysis was performed using clinical data obtained from 3 neuroscience centers in Western Saudi Arabia in the period 2014-2019. The sample size included 663 adult and pediatric cases from the local and expatriate populations diagnosed with CNS tumors. The distributions of age, sex, clinical presentation, tumor location, type of surgery, histological subtype, genetic characteristics, and recurrence rate were explored. RESULTS: The analysis included 500 adult cases and 163 pediatric cases up to 18 years of age with a male-to-female ratio of 1.16. The mean age at diagnosis was 38.0±22.6 years. The supratentorium was the most common location (n=515, 77.7%). Most patients presented with headache (n=298, 44.9%), followed by a focal neurological deficit (19.9%). The most common primary CNS tumor was glioblastoma (n=234, 35.3%), followed by meningioma (n=100, 15.1%). The recurrence rate after surgery was estimated to be 40.9% among all CNS tumors. CONCLUSIONS: This is the first tumor registry of Western Province of Saudi Arabia that describes the distribution of primary CNS tumors and highlights their epidemiological matrix. Several incidence trends in terms of histological type, age group, sex, location, and recurrence were determined, and some genetic characteristics were recognized.

The Impact of IDH1 Mutation and MGMT Promoter Methylation on Recurrence-Free Interval in Glioblastoma Patients Treated With Radiotherapy and Chemotherapeutic Agents.

The aim of this study is to investigate the relationship between isocitrate dehydrogenase-1 (IDH1) mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with recurrence-free interval in glioblastoma patients treated with chemoradiotherapies. Clinical data were collected from 82 patients with totally resected glioblastoma and treated with adjuvant therapies from 2014 to 2019. IDH1 mutation was assessed by immunohistochemistry and MGMT promoter methylation was assessed by different sequencing methods. IDH1 mutation was present in 32 cases and 50 cases were IDH1 wildtype; 54 and 28 patients had unmethylated and methylated MGMT promoter, respectively, Of the 82 patients, 62 patients received chemoradiotherapy while 20 patients only received radiation. Approximately, 61% of patients had a tumor recurrence after 1 year, and 39% showed a recurrence before 1 year of treatment. There was no significant relationship between IDH1 mutation and MGMT promoter methylation (p-value = 0.972). Patients with IDH1 mutation and their age <50 years showed a significant difference in recurrence-free interval (p-value = 0.014). Difference in recurrence-free interval was also statistically observed in patients with unmethylated MGMT promoter and treated with chemoradiotherapies (p-value = 0.031), by which they showed a late tumor recurrence (p-value = 0.016). This revealed that IDH1 mutation and MGMT methylation are independent prognostic factors in glioblastoma. Although IDH1-mutant glioblastomas showed late tumor recurrence in patients less than 50 years old, the type of treatment modalities may not show additional beneficial outcome. Patients with unmethylated MGMT and IDH1 mutation, treated with different chemoradiotherapies, showed a late tumor recurrence.

Sensitivity Assessment of Wilms Tumor Gene (WT1) Expression in Glioblastoma using qPCR and Immunohistochemistry and its Association with IDH1 Mutation and Recurrence Interval.

PURPOSE: Wilms tumor 1 (WT1) gene has recently shown a role in gliomagenesis, making it a potential immunotherapy target in glioblastomas. We aimed to investigate the most sensitive method to detect WT1 expression in glioblastoma and explore the relationship between WT1 expression, IDH1 mutation and recurrence interval. PATIENTS AND METHODS: Clinical data were collected from 44 patients with glioblastomas, treated with adjuvant therapies. WT1 expression was assessed in all cases using immunohistochemistry (IHC), while its gene expression was assessed in 13 clustered samples using polymerase chain reaction (qPCR). IDH1 mutation was assessed using IHC. The sensitivity between IHC and RT-qPCR was examined. Kaplan-Meier curves were used to compare the recurrence-free interval (RFI) between IDH1 and WT1 expression groups. RESULTS: IDH1wildtype was found in 26 cases (59.1%) and the remaining 18 cases (40.9%) were IDH1mutant. Through IHC, WT1 was overexpressed in 32 cases (72.7%), partially expressed in 9 cases (20.5%) and not expressed in only 3 cases. For the 13 cases tested by qPCR, 6 cases showed WT1 upregulation and 7 cases showed WT1 downregulation. There was no significant difference in WT1 expression among cases with different RNA concentrations regardless the testing method (p-value >0.05). However, the difference between IHC and qPCR was significant. IDH1mutant cases with WT1 overexpression showed significant difference in RFI (p-value =0.048). CONCLUSION: Parallel testing for WT1 expression using IHC and qPCR is not reliable. However, IHC provides more accurate results. Moreover, IDH1mutant glioblastomas with WT1 overexpression are associated with late RFI particularly if temozolomide with additional chemotherapies are used.

Endoscopic transnasal suprasellar approach for anterior clinoidal meningioma: A case report and review of the literature.

BACKGROUND: Anterior clinoidal meningiomas (ACM) are traditionally approached through transcranial routes. Due to their tendency to extend laterally and their proximity to vital neurovascular structures, the endoscopic transnasal suprasellar approach is still questionable. We present and describe an ACM case that underwent an endoscopic transnasal suprasellar approach, and provide a review of the literature and operative technique. CASE DESCRIPTION: A 56 year-old lady who presented with chronic left-sided decreased vision. Brain imaging revealed a lesion measuring 9 × 10 × 11 mm attached to the left anterior clinoid process (ACP) and extending to the left optic canal. Lesion was compressing the left optic nerve (ON) and abutting the supraclinoid part of the left internal carotid artery (ICA). Utilizing the endoscopic transnasal suprasellar approach, the meningioma was resected and the optic canal was decompressed. Reconstruction was achieved using fascia lata, vomer bone, and nasoseptal flap. A lumbar drain was inserted perioperatively. Patient had no perioperative morbidity and retained vision in the affected eye. CONCLUSIONS: Resection of selected ACMs can be safely achieved utilizing the endoscopic transnasal suprasellar approach. Although the literature lacks long-term outcome comparison between the transnasal and the traditional transcranial approaches, specifically addressing ACMs, this technique is becoming more popular over the last decade. More efforts should be directed towards implementing and reporting the endoscopic transnasal suprasellar approach for meningiomas of the anterior clinoid process.